The Superoxide Reductase from the Early Diverging Eukaryote Giardia Intestinalis
Unlike superoxide dismutases (SODs), superoxidereductases (SORs) eliminate superoxide anion (O{sub 2}{sup {sm_bullet}-}) not through its dismutation, but via reduction to hydrogen peroxide (H{sub 2}O{sub 2}) in the presence of an electron donor. The microaerobic protist Giardia intestinalis, responsible for a common intestinal disease in humans, though lacking SOD and other canonical reactive oxygen species-detoxifying systems, is among the very few eukaryotes encoding a SOR yet identified. In this study, the recombinant SOR from Giardia (SOR{sub Gi}) was purified and characterized by pulse radiolysis and stopped-flow spectrophotometry. The protein, isolated in the reduced state, after oxidation by superoxide or hexachloroiridate(IV), yields a resting species (T{sub final}) with Fe{sup 3+} ligated to glutamate or hydroxide depending on pH (apparent pK{sub a} = 8.7). Although showing negligible SOD activity, reduced SOR{sub Gi} reacts with O{sub 2}{sup {sm_bullet}-} with a pH-independent second-order rate constant k{sub 1} = 1.0 x 10{sup 9} M{sup -1} s{sup -1} and yields the ferric-(hydro)peroxo intermediate T{sub 1}; this in turn rapidly decays to the T{sub final} state with pH-dependent rates, without populating other detectable intermediates. Immunoblotting assays show that SOR{sub Gi} is expressed in the disease-causing trophozoite of Giardia. We propose that the superoxide-scavenging activity of SOR in Giardia may promote the survival of this air-sensitive parasite in the fairly aerobic proximal human small intestine during infection.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE SC OFFICE OF SCIENCE (SC)
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1040547
- Report Number(s):
- BNL-94884-2011-JA; FRBMEH; R&D Project: CO-004; TRN: US1202495
- Journal Information:
- Free Radical Biology and Medicine, Vol. 51, Issue 8; ISSN 0891-5849
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
ANIONS
BINDING ENERGY
DISEASES
ELECTRONS
HYDROGEN PEROXIDE
HYDROXIDES
OXIDATION
OXIDOREDUCTASES
OXYGEN
PARASITES
RADIOLYSIS
SMALL INTESTINE
SPECTROPHOTOMETRY
SUPEROXIDE DISMUTASE
VALENCE
pulse radiolysis
superoxide